Thermoplastic elastomeric poly(ortho ester) block or random copolymers in which the reaction products of a diketene diacetal with structurally rigid diols or with diols containing at least one functional group which produces hydrogen bonding or other association to form the hard, rigid segments in a copolymer having alternating rigid and flexible segments and in which the flexible segments are synthesized by the reaction of a diketene diacetal with diols that are non-polar, are conformationally flexible and are essentially hydrocarbon in character. These copolymers are bioerodible and are useful in the fabrication of medical devices (e.g. implants, sutures) and in the fabrication of pharmaceutical dosage forms for the controlled release of drug substances inside the bodies of humans and animals. These polymers are suitable as carriers or matrices for drugs and other beneficial agents. These polymers upon contact with the environment in which they are used, degrade and release the drug biologically active agent in a predictable manner.
Poly(ortho ester) polymers are generally known in the art and are described, for example, in U.S. Pat. No. 4,304,767. The art shows that poly(ortho ester) polymers can be made by the acid catalyzed condensation reaction of diketene diacetals with diols.
It is an object of the present invention to provide bioerodible poly(ortho ester) block or random copolymers which erode in a predictable manner, are elastomeric and which are processable by thermoplastic techniques. It is another object of the present invention to provide bioerodible poly(ortho ester) copolymers that are more hydrophilic in nature than former poly(ortho ester) compositions.
Both of the above mentioned objects are accomplished by synthesizing copolymers which incorporate specific types of diols in their backbones. These diols are capable of producing strong interactions between adjacent poly(ortho ester) segments in two different ways:
(1) The diols may have rigid and highly symmetrical structures that are apt to fit easily in a crystal lattice. Thus the diols from adjacent polymer chains tend to associate with each other to form a crystalline zone in the polymer which acts as a physical tie between polymer chains. PA0 (2) The diols may contain functionalities capable of engaging in hydrogen bonding, i.e., amides, urethanes, ureas and imides. This hydrogen bonding provides tie points between adjacent polymer chains. PA0 (A) a diketene diacetal; PA0 (B) a long-chain- non-polar, flexible diol containing 4 to 22 carbon atoms; and PA0 (C) diol selected from the group consisting of: PA0 (A) 60 to 95%, by weight, based on the total weight of the polymer produced, of a flexible segment prepared from a diketene diacetal and a long chain, non-polar, flexible diol containing 4 to 22 carbons atoms; and PA0 (B) 5 to 40%, by weight, based on the total weight of the polymer produced, of a rigid segment prepared from a diketene diacetal and a rigid diol selected from the group consisting of:
Bioerodible thermoplastic elastomers are highly desirable materials from a standpoint of their ease of fabrication: they can be extruded, injection molded, transfer molded, calendered and vacuum formed. Those elastomers which are not crosslinked may be reprocessed without deterioration. Some of the proposed uses of these materials are as bioerodible material of construction for controlled release devices or biomedical applications (e.g. sutures), and as controlled erosion pharmaceutical coatings.